{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T19:41:49Z","timestamp":1783712509488,"version":"3.55.0"},"reference-count":59,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DR455\/3-1"],"award-info":[{"award-number":["DR455\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004563","name":"Bavarian State Ministry of Education Science and the Arts","doi-asserted-by":"publisher","award":["Herstellung und biophysikalische Charakterisierung dreidimensionaler Gewebe - CANTER"],"award-info":[{"award-number":["Herstellung und biophysikalische Charakterisierung dreidimensionaler Gewebe - CANTER"]}],"id":[{"id":"10.13039\/501100004563","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ageing or obesity are risk factors for protein aggregation in the endoplasmic reticulum (ER) of chondrocytes. This condition is called ER stress and leads to induction of the unfolded protein response (UPR), which, depending on the stress level, restores normal cell function or initiates apoptotic cell death. Here the role of ER stress in knee osteoarthritis (OA) was evaluated. It was first tested in vitro and in vivo whether a knockout (KO) of the protein disulfide isomerase ERp57 in chondrocytes induces sufficient ER stress for such analyses. ER stress in ERp57 KO chondrocytes was confirmed by immunofluorescence, immunohistochemistry, and transmission electron microscopy. Knee joints of wildtype (WT) and cartilage-specific ERp57 KO mice (ERp57 cKO) were analyzed by indentation-type atomic force microscopy (IT-AFM), toluidine blue, and immunofluorescence\/-histochemical staining. Apoptotic cell death was investigated by a TUNEL assay. Additionally, OA was induced via forced exercise on a treadmill. ER stress in chondrocytes resulted in a reduced compressive stiffness of knee cartilage. With ER stress, 18-month-old mice developed osteoarthritic cartilage degeneration with osteophyte formation in knee joints. These degenerative changes were preceded by apoptotic death in articular chondrocytes. Young mice were not susceptible to OA, even when subjected to forced exercise. This study demonstrates that ER stress induces the development of age-related knee osteoarthritis owing to a decreased protective function of the UPR in chondrocytes with increasing age, while apoptosis increases. Therefore, inhibition of ER stress appears to be an attractive therapeutic target for OA.<\/jats:p>","DOI":"10.3390\/ijms23010182","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T08:38:46Z","timestamp":1640335126000},"page":"182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["ER Stress in ERp57 Knockout Knee Joint Chondrocytes Induces Osteoarthritic Cartilage Degradation and Osteophyte Formation"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2138-0447","authenticated-orcid":false,"given":"Yvonne","family":"Rellmann","sequence":"first","affiliation":[{"name":"Institute of Physiological Chemistry and Pathobiochemistry, Waldeyerstra\u00dfe 15, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elco","family":"Eidhof","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry and Pathobiochemistry, Waldeyerstra\u00dfe 15, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Hansen","sequence":"additional","affiliation":[{"name":"Institute of Musculoskeletal Medicine, University Hospital M\u00fcnster, Albert-Schweitzer-Campus 1, Building D3, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Fleischhauer","sequence":"additional","affiliation":[{"name":"Center for Applied Tissue Engineering and Regenerative Medicine-CANTER, Munich University of Applied Sciences, 80335 Munich, Germany"},{"name":"Center for Nanoscience-CeNS, 80335 Munich, Germany"},{"name":"Department for Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), University Hospital, LMU Munich, 80335 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Vogel","sequence":"additional","affiliation":[{"name":"Center for Applied Tissue Engineering and Regenerative Medicine-CANTER, Munich University of Applied Sciences, 80335 Munich, Germany"},{"name":"Center for Nanoscience-CeNS, 80335 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9413-0310","authenticated-orcid":false,"given":"Hauke","family":"Clausen-Schaumann","sequence":"additional","affiliation":[{"name":"Center for Applied Tissue Engineering and Regenerative Medicine-CANTER, Munich University of Applied Sciences, 80335 Munich, Germany"},{"name":"Center for Nanoscience-CeNS, 80335 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3569-6557","authenticated-orcid":false,"given":"Attila","family":"Aszodi","sequence":"additional","affiliation":[{"name":"Department for Orthopaedics and Trauma Surgery, Musculoskeletal University Center Munich (MUM), University Hospital, LMU Munich, 80335 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1267-8217","authenticated-orcid":false,"given":"Rita","family":"Dreier","sequence":"additional","affiliation":[{"name":"Institute of Physiological Chemistry and Pathobiochemistry, Waldeyerstra\u00dfe 15, 48149 Muenster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Grassel, S., Zaucke, F., and Madry, H. (2021). Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology. J. Clin. Med., 10.","DOI":"10.3390\/jcm10091938"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16072","DOI":"10.1038\/nrdp.2016.72","article-title":"Osteoarthritis","volume":"2","author":"Barr","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s11420-011-9248-6","article-title":"Osteoarthritis as a whole joint disease","volume":"8","author":"Poole","year":"2012","journal-title":"HSS J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/978-1-61779-367-7_21","article-title":"Human chondrocyte cultures as models of cartilage-specific gene regulation","volume":"806","author":"Otero","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1002\/jcp.21258","article-title":"Osteoarthritis","volume":"213","author":"Goldring","year":"2007","journal-title":"J. Cell Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8421394","DOI":"10.1155\/2018\/8421394","article-title":"Different Forms of ER Stress in Chondrocytes Result in Short Stature Disorders and Degenerative Cartilage Diseases: New Insights by Cartilage-Specific ERp57 Knockout Mice","volume":"2018","author":"Rellmann","year":"2018","journal-title":"Oxid Med. Cell Longev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1093\/embo-reports\/kvf202","article-title":"Structural organization of the endoplasmic reticulum","volume":"3","author":"Voeltz","year":"2002","journal-title":"EMBO Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-020-0250-z","article-title":"Mechanisms, regulation and functions of the unfolded protein response","volume":"21","author":"Hetz","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/ncb3184","article-title":"Proteos.stasis control by the unfolded protein response","volume":"17","author":"Hetz","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tsang, K.Y., Chan, D., Cheslett, D., Chan, W.C., So, C.L., Melhado, I.G., Chan, T.W., Kwan, K.M., Hunziker, E.B., and Yamada, Y. (2007). Surviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function. PLoS Biol., 5.","DOI":"10.1371\/journal.pbio.0050044"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hughes, A., Oxford, A.E., Tawara, K., Jorcyk, C.L., and Oxford, J.T. (2017). Endoplasmic Reticulum Stress and Unfolded Protein Response in Cartilage Pathophysiology; Contributing Factors to Apoptosis and Osteoarthritis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030665"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1002\/art.1780350715","article-title":"Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy","volume":"35","author":"Kirsch","year":"1992","journal-title":"Arthritis Rheum."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.pharmthera.2017.07.011","article-title":"Multifunctional molecule ERp57: From cancer to neurodegenerative diseases","volume":"181","author":"Hettinghouse","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.biocel.2010.01.009","article-title":"ERp57, a multifunctional endoplasmic reticulum resident oxidoreductase","volume":"42","author":"Coe","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1126\/science.275.5296.86","article-title":"Interaction of the thiol-dependent reductase ERp57 with nascent glycoproteins","volume":"275","author":"Oliver","year":"1997","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/sj.emboj.7601505","article-title":"ERp57 is essential for efficient folding of glycoproteins sharing common structural domains","volume":"26","author":"Jessop","year":"2007","journal-title":"EMBO J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/sj.embor.7400311","article-title":"The human protein disulphide isomerase family: Substrate interactions and functional properties","volume":"6","author":"Ellgaard","year":"2005","journal-title":"EMBO Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1002\/jbmr.2484","article-title":"ER Stress During the Pubertal Growth Spurt Results in Impaired Long-Bone Growth in Chondrocyte-Specific ERp57 Knockout Mice","volume":"30","author":"Linz","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1186\/ar3117","article-title":"Hypertrophic differentiation of chondrocytes in osteoarthritis: The developmental aspect of degenerative joint disorders","volume":"12","author":"Dreier","year":"2010","journal-title":"Arthritis Res. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1016\/j.bbamcr.2013.05.020","article-title":"Detection and quantification of endoplasmic reticulum stress in living cells using the fluorescent compound, Thioflavin T","volume":"1833","author":"Beriault","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1016\/j.bpj.2010.02.013","article-title":"Micro- and nanomechanical analysis of articular cartilage by indentation-type atomic force microscopy: Validation with a gel-microfiber composite","volume":"98","author":"Loparic","year":"2010","journal-title":"Biophys. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.matbio.2015.10.001","article-title":"Structural and mechanical properties of the proliferative zone of the developing murine growth plate cartilage assessed by atomic force microscopy","volume":"50","author":"Prein","year":"2016","journal-title":"Matrix Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nnano.2008.410","article-title":"Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy","volume":"4","author":"Stolz","year":"2009","journal-title":"Nat. Nanotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.joca.2006.11.006","article-title":"Osteophytes: Relevance and biology","volume":"15","year":"2007","journal-title":"Osteoarthr. Cartil."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R124","DOI":"10.1186\/ar2013","article-title":"Expression profiling of metalloproteinases and their inhibitors in synovium and cartilage","volume":"8","author":"Davidson","year":"2006","journal-title":"Arthritis Res. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1136\/ard.56.9.542","article-title":"Gene expression of matrix metalloproteinases 1, 3, and 9 by chondrocytes in osteoarthritic human knee articular cartilage is zone and grade specific","volume":"56","author":"Freemont","year":"1997","journal-title":"Ann. Rheum. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"21712","DOI":"10.1016\/S0021-9258(19)36670-0","article-title":"Matrix metalloproteinase 9 (92-kDa gelatinase\/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties","volume":"267","author":"Okada","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nature03369","article-title":"Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis","volume":"434","author":"Glasson","year":"2005","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/nature03417","article-title":"ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro","volume":"434","author":"Stanton","year":"2005","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hartmann, B., Marchi, G., Alberton, P., Farkas, Z., Aszodi, A., Roths, J., and Clausen-Schaumann, H. (2020). Early Detection of Cartilage Degeneration: A Comparison of Histology, Fiber Bragg Grating-Based Micro-Indentation, and Atomic Force Microscopy-Based Nano-Indentation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197384"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.3892\/ijmm.2015.2158","article-title":"The utility of mouse models to provide information regarding the pathomolecular mechanisms in human genetic skeletal diseases: The emerging role of endoplasmic reticulum stress (Review)","volume":"35","author":"Briggs","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s13075-019-1988-6","article-title":"Cartilage endoplasmic reticulum stress may influence the onset but not the progression of experimental osteoarthritis","volume":"21","author":"Kung","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/j.ajpath.2021.05.016","article-title":"Primary Osteoarthritis Early Joint Degeneration Induced by Endoplasmic Reticulum Stress Is Mitigated by Resveratrol","volume":"191","author":"Hecht","year":"2021","journal-title":"Am. J. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6725","DOI":"10.1074\/jbc.M109.054015","article-title":"ERp57 modulates STAT3 signaling from the lumen of the endoplasmic reticulum","volume":"285","author":"Coe","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"625497","DOI":"10.3389\/fcell.2021.625497","article-title":"Chondrocyte Aging: The Molecular Determinants and Therapeutic Opportunities","volume":"9","author":"Ramasamy","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.14336\/AD.2019.1130","article-title":"Age-Related Decline in Expression of Molecular Chaperones Induces Endoplasmic Reticulum Stress and Chondrocyte Apoptosis in Articular Cartilage","volume":"11","author":"Tan","year":"2020","journal-title":"Aging Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3389\/fphys.2012.00263","article-title":"The endoplasmic reticulum stress response in aging and age-related diseases","volume":"3","author":"Brown","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1515\/REVNEURO.2009.20.1.23","article-title":"The endoplasmic reticulum stress response and aging","volume":"20","author":"Naidoo","year":"2009","journal-title":"Rev. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.cmet.2018.08.014","article-title":"The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality","volume":"28","author":"Chaudhuri","year":"2018","journal-title":"Cell Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s001250051591","article-title":"Advanced glycation end-products: A review","volume":"44","author":"Singh","year":"2001","journal-title":"Diabetologia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1111\/febs.12170","article-title":"Intracellular accumulation of advanced glycation end products induces apoptosis via endoplasmic reticulum stress in chondrocytes","volume":"280","author":"Yamabe","year":"2013","journal-title":"FEBS J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1007\/s00535-009-0193-9","article-title":"The formation of intracellular glyceraldehyde-derived advanced glycation end-products and cytotoxicity","volume":"45","author":"Takino","year":"2010","journal-title":"J. Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1515\/cclm-2012-0826","article-title":"Advanced glycation end-products induce endoplasmic reticulum stress in human aortic endothelial cells","volume":"52","author":"Adamopoulos","year":"2014","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1016\/j.bbamcr.2012.08.021","article-title":"Endoplasmic reticulum stress induces the expression of COX-2 through activation of eIF2alpha, p38-MAPK and NF-kappaB in advanced glycation end products stimulated human chondrocytes","volume":"1823","author":"Rasheed","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/art.21523","article-title":"Activation of receptor for advanced glycation end products in osteoarthritis leads to increased stimulation of chondrocytes and synoviocytes","volume":"54","author":"Steenvoorden","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fphys.2013.00121","article-title":"Inflammatory markers associated with osteoarthritis after destabilization surgery in young mice with and without Receptor for Advanced Glycation End-products (RAGE)","volume":"4","author":"Larkin","year":"2013","journal-title":"Front. Physiol"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5818","DOI":"10.1096\/fj.201902746R","article-title":"High-fat diet induces endoplasmic reticulum stress to promote chondrocyte apoptosis in mouse knee joints","volume":"34","author":"Tan","year":"2020","journal-title":"Faseb J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.metabol.2016.05.002","article-title":"Endoplasmic reticulum stress in obesity and obesity-related disorders: An expanded view","volume":"65","author":"Pagliassotti","year":"2016","journal-title":"Metabolism"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6404035","DOI":"10.1155\/2019\/6404035","article-title":"4-Phenylbutyric Acid Reduces Endoplasmic Reticulum Stress in Chondrocytes That Is Caused by Loss of the Protein Disulfide Isomerase ERp57","volume":"2019","author":"Rellmann","year":"2019","journal-title":"Oxid Med. Cell Longev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e37673","DOI":"10.7554\/eLife.37673","article-title":"Inhibiting the integrated stress response pathway prevents aberrant chondrocyte differentiation thereby alleviating chondrodysplasia","volume":"7","author":"Wang","year":"2018","journal-title":"eLife"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1172\/JCI93094","article-title":"Increased intracellular proteolysis reduces disease severity in an ER stress-associated dwarfism","volume":"127","author":"Mullan","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1002\/art.11341","article-title":"Molecular phenotyping of human chondrocyte cell lines T\/C-28a2, T\/C-28a4, and C-28\/I2","volume":"48","author":"Finger","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1111\/j.1582-4934.2007.00138.x","article-title":"Researching into the cellular shape, volume and elasticity of mesenchymal stem cells, osteoblasts and osteosarcoma cells by atomic force microscopy","volume":"12","author":"Docheva","year":"2008","journal-title":"J. Cell Mol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1038\/s41563-020-00894-0","article-title":"Basement membrane stiffness determines metastases formation","volume":"20","author":"Reuten","year":"2021","journal-title":"Nat. Mater."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1136\/annrheumdis-2016-209319","article-title":"Forced exercise-induced osteoarthritis is attenuated in mice lacking the small leucine-rich proteoglycan decorin","volume":"76","author":"Gronau","year":"2017","journal-title":"Ann. Rheum. Dis"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"191","DOI":"10.2144\/btn-2018-0021","article-title":"The use of commercially available adhesive tapes to preserve cartilage and bone tissue integrity during cryosectioning","volume":"65","author":"Serowoky","year":"2018","journal-title":"Biotechniques"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.joca.2010.05.025","article-title":"The OARSI histopathology initiative\u2014Recommendations for histological assessments of osteoarthritis in the mouse","volume":"18","author":"Glasson","year":"2010","journal-title":"Osteoarthr. Cartil."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/182\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:52:54Z","timestamp":1760169174000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,24]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23010182"],"URL":"https:\/\/doi.org\/10.3390\/ijms23010182","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,24]]}}}